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Does Hydroquinone Have a Dark Side?

hydroquinoneThey were once mistakenly thought to be caused by a disease of the liver, so they are called “liver spots.” Actually these skin blemishes are caused by a buildup of the skin pigment melanin and are associated with aging and long-term exposure to ultraviolet light. Technically referred to as “Lentigo senilis,” these hyperpigmented spots usually just present a cosmetic problem unless they develop irregular borders and undergo a colour change, in which case they need to be evaluated by a physician. People bothered by such “senile freckles” can look to hydroquinone for help.

When applied as an ingredient in a skin cream, this chemical inhibits the activity of tyrosinase, an enzyme that is necessary for the formation of melanin. This brings up three questions. How well does hydroquinone work, what concentration is needed, and what risks, if any, does its use present? Hydroquinone does work, and its efficacy, as is to be expected, is dose related. Need a minimum of 1% in a cream to see any result, and really significant effects kick in at 4%. In the U.S., hydroquinone is available in over the counter products at concentrations up to 2%, anything more than that requires a prescription. In Europe and in Canada all hydroquinone products require a prescription. Why the difference?

Different regulatory agencies arrive at decisions in different ways. In this case, Europe and Canada look at worst case scenarios while the U.S. evaluates hydroquinone based on its actual use in cosmetics. Rat feeding studies have suggested that hydroquinone may be carcinogenic, although this is contentious. In humans, in rare cases, accidental ingestion of photographic developer fluid containing hydroquinone has resulted in toxic reactions, but in a controlled trial with human volunteers, ingestion of 300-500 mgs daily for months produced no observable effects. As far as topical application goes, no systemic reaction has ever been noted, and no link to skin cancer has ever been found. But there is a chance of skin irritation, especially if sun protection is not used after application, as well as a rarely seen blue discoloration known as “ochronosis.” With higher concentrations there is the possibility of losing too much pigment resulting in white spots. It is mainly for the latter reasons, and some concern that hydroquinone has not been studied with enough rigour, that Canada and Europe are concerned about over-the-counter availability.

But aside from hydroquinone products that have been adulterated with mercury compounds, which has happened in Africa, no significant problems with 2% solutions have cropped up. Hydroquinone also occurs in nature, found in the bearberry, madder and mulberry plants, extracts of which are touted as “natural skin lightening agents.” These do work, but whatever issues arise with hydroquinone apply to these preparations as well. The fact that the hydroquinone comes from a natural source is irrelevant. Basically, 2% hydroquinone preparations, no matter what the source, can reduce age spots effectively and the alarm sounded by some activist organizations about such products is not backed up by evidence.

 

Joe Schwarcz

Want to keep Alzheimer’s disease at bay? Who wouldn’t? So let’s surf the web! Keep in mind that almost every study encountered is riddled with “ifs” and “maybes.”

Screen Shot 2015-03-24 at 9.10.52 PMSticking to the Mediterranean diet – low in meat and dairy products, high in fruits, vegetables, legumes, cereals and fish – would seem to be a good start. A study of close to 500 seniors with mild cognitive impairment showed a reduced risk of developing Alzheimer’s with adherence to the Mediterranean diet. Eating fish is an important feature, with studies showing that people with higher blood levels of omega-3 fatty acids tend to have larger brain volumes in old age. It seems fish oil protects the brain’s hippocampus region, the area where shrinkage is associated with dementia.

But watch how you cook your meals. Grilling, frying or broiling produces “advanced glycation end products,” which have been linked to inflammation, insulin resistance and Alzheimer’s disease. And watch that sugar intake. A study of some 900 subjects with no cognitive problems found that within four years, 200 began to show mild cognitive impairment. Those with the highest sugar intake were 1.5 times more likely to have memory problems than those with the lowest intake. Diets containing walnuts as well as strawberry or blueberry extracts were found to reverse several parameters of brain aging, as well as age-related motor and cognitive deficits. As long as you are an aging rat.

Might not be a bad idea to add a little Indian flavour to the diet in the form of turmeric, a common spice in curry. Curcumin, its major component, has been linked with slower cognitive decline and reduced amyloid beta plaques, one of the major causes of Alzheimer’s disease. Grape seed extract appears to have the same effect, at least in mice. People with Alzheimer’s tend to have lower vitamin D than those without the disease, and better cognitive test results have been linked with higher vitamin D levels. A supplement may be in order.

People who drink three to five cups of coffee a day in their midlife years have a 65-per-cent lower chance of developing dementia and Alzheimer’s disease compared with those who drink little coffee. Green tea will do as well since its epigallocatechin-3-gallate content has been shown to prevent the buildup of beta-amyloid aggregates, at least in lab experiments. In non-smoking women, moderate alcohol consumption reduces the risk of Alzheimer’s. And consider fruit juices. People drinking them three or more times per week were 76 per cent less likely to develop Alzheimer’s than those who drank less than one serving per week. Pomegranate juice may be particularly beneficial.

Instead of thinking about what to eat or drink, perhaps we should think about infusing protective factors directly into our blood. Studies have shown that a transfusion of young mouse blood into older animals can improve cognition. Focus is on a protein in blood plasma called “growth differentiation factor 11 (GDF11)” that declines with age both in mice and in humans. Drinking young blood won’t do.

You want to make sure you breathe clean air. Women who live in areas with the worst quality air score perform more poorly on tests of memory and thinking than those who live in cleaner areas. On the other hand, there is a correlation between strict hygiene and sanitation methods as practiced in wealthy countries and the prevalence of Alzheimer’s disease. The “hygiene hypothesis” is gaining traction when it comes to allergies and asthma, with the theory being that exposure to bacteria, viruses and worms early in life primes the development of a healthy immune system. Some researchers suggest that the deposition of proteins in the nervous system, one of the hallmarks of Alzheimer’s, is a result of an immune system gone astray.

And remember to brush your teeth. A study that looked at 100 sets of twins, one with Alzheimer’s and the other unaffected, found that the twin with dementia was four times more likely to have had mid-life gum disease. Playing chess, reading newspapers and engaging the brain in other tasks can significantly reduce the risk of Alzheimer’s in later life, as can physical exercise. Be conscientious. Subjects who enthusiastically agreed with statements such as: “I work hard to accomplish my goals,” “I strive for excellence in everything I do,” “I keep my belongings clean and neat” and “I’m pretty good about pacing myself so as to get things done on time,” were less likely to develop Alzheimer’s disease.

Finally, I came across a paper I really liked. A brain scan study at the University of California concluded that surfing the web increases brain activity more than reading a book. What can I say? Maybe.

Joe Schwarcz

Pills for the Brain

Screen Shot 2015-01-15 at 9.11.26 AMPop this pill and improve your memory. Swallow that one and reduce your cognitive decline. We see ads for such products all the time and I suspect they will increase as the baby boomers reach senior citizenhood. The most popular brain boosting supplements are fish oil pills and they are also probably the best studied ones. The results are not encouraging. When all the studies are pooled, we are left with the possibility of a barely significant improvement in recalling lists of words soon after they have been learned, but the effect does not last. Extracts of the ginkgo biloba tree are also popular, and here the prospects are even dimmer. There is no impact on memory, despite claims of increased circulation in the brain. And ginkgo can interfere with the action of anticoagulants and has also been shown to be an animal carcinogen.

B vitamins are also sold with claims of enhancing memory, usually rationalized by their reduction of homocysteine, a chemical in the blood that may affect circulation in the brain. No benefits from B vitamin intake have been demonstrated when it comes to memory or cognitive function except in the case of people who have high homocysteine levels due to a diet that is very low in B vitamins. There is some concern that folic acid, one of the B vitamins, may spur the growth of polyps in the colon at doses greater than 800 micrograms a day. Phosphatidyl serine is a natural component of nerve cell membranes and its promoters argue that a deficiency leads to impaired communication between nerve cells which in turn impairs cognitive function. Sounds reasonable, except that proper controlled trials have come up empty. The same goes for vinpocetine, a compound originally isolated from the lesser periwinkle plant by Hungarian chemist Csaba Szantay in 1975. It is widely used in Europe to treat strokes and memory problems with claims of increased circulation to the brain. It does indeed increase circulation, much like ginkgo, but there is no compelling evidence for memory improvement.

People with failing memory and worried about Alzheimer’s disease are sometimes seduced by advertisements for Huperzine A, extracted from a type of moss. Some studies have shown that it increases levels of acetylcholine in the brain, a chemical that is in short supply in Alzheimer’s. But despite increasing acetylcholine, aside from a few questionable studies in China, there is no evidence that it improves memory. Unfortunately when it comes to memory pills, they are best forgotten. There is, however, hope that a nasal spray containing insulin can increase the absorption of glucose into brain cells and improve cognitive function. But in the meantime, the best bet to maintain good brain function is to monitor blood glucose and blood pressure, eat a diet rich in fruits, vegetables and whole grains, and low in simple carbs and saturated fat. And don’t forget that physical exercise also exercises your brain.

Dr. Joe Schwarcz

Weighing the benefits of tea

tea“Get in here and sit your ass down!”

Not exactly what you expect to hear when you are peacefully walking in San Francisco’s Chinatown. But the boisterous elderly Chinese gentleman seemed charismatic enough, and the establishment didn’t look like an opium den. Indeed it wasn’t. It was a tea house. But not your ordinary tea house.

We quickly found ourselves plunked down at a long counter along with a number of other tourists who had been dragged in from the street.

“It’s not for taste, it’s for health,” began “Uncle Gee,” who I was to learn was a local institution.

“Eighty-four years old,” he boasted, and “in perfect health!”

“Drink eight cups of tea a day; never coffee!”

“Tea full of antioxidants against cancer!”

Not only were we treated to a lecture on the “science” and history of tea, we were also ordered to try about half a dozen varieties.

“Never use boiling water, the tea will scream,” and so did he. “Don’t even dream about adding milk or sugar.”

“Steep for only twenty seconds!”

We sipped rosebud tea from Iran to ward off insomnia, and “puerh” for weight loss and heart problems. Next came Blue People Ginseng Oolong. I don’t know why the “blue.” I looked around and none of the people drinking it were turning blue. Everyone enjoyed that one. It was a truly different taste, with a hint of licorice, “a party-in-your-mouth tea,” we were told.

As our taste buds were partying, I glanced around at the dozens and dozens of jars, all with intriguing names.

“Monkey-picked green tea” for “cleansing the body” caught my attention. It wasn’t clear if this was to be applied to the outside or the inside of the body, or how the monkeys had been trained to pick tea. I wanted to ask if this was just monkey business, but didn’t dare. I did muster up enough courage to ask Uncle Gee about his favourite tea, the one that kept him young and so full of whatever. He quickly pointed to “Angel Green tea.”

“Good for high blood pressure, cholesterol, diabetes and detox.”

At $160 a pound, I suspect good for profits too, although there was no “hard sell.” The tea bash ended with Uncle Gee telling us that while we were strangers when we came in, we were now part of the family. How could I resist buying some Angel Green and Blue People?

We’ve been enjoying both teas ever since, but other than frolicking taste buds, I can’t vouch for any benefits. But tea leaves do contain more than 700 compounds, many with potential biological activity. It is the “polyphenols,” the “catechins” in particular, that have aroused researchers’ interest enough to generate a truckload of studies.

When rats are fed green-tea leaves, their blood cholesterol and triglycerides go down. Levels of such enzymes as superoxide dismutase, catalase and glutathione-S-transferase, all involved in removing foreign chemicals from the body, go up. The rats are also less prone to weight gain, apparently because of an increase in metabolism.

But in these studies, the rats consume far more tea on a weight basis than people ever can. As far as human-population studies go, some show a decrease in colon, breast, stomach and prostate cancer; but others don’t. The studies are neither consistent nor convincing, which is not surprising given that there are numerous varieties of tea, their chemical profiles depending on the type of tea, where it is grown and how it is harvested, stored and processed. Most of the epidemiological studies that have shown health benefits have focused on Asian populations, where tea consumption is much greater than in North America, and lifestyles are very different.

Laboratory studies have also been carried out with various tea components. For example, heterocyclic aromatic amines, compounds produced when meat is cooked at a high temperature, are less likely to trigger cancer in the presence of the polyphenols theaflavine gallate and epigallocatechin gallate. Such findings, along with the suggestion of increased rates of metabolism, have led to the sale of various dietary supplements based on tea extracts. Why go to the trouble of drinking tea when you can just pop a “cancer-fighting, fat-burning” pill?

But here we run into a problem. Such dietary supplements are poorly regulated; and the amount of catechins they contain can be far greater than that available from drinking tea. The high doses may indeed help to increase metabolism and result in weight loss, but the cost can be high. Just ask the teenager who walked into the emergency room at Texas Children’s Hospital with his chest, face and eyes bright yellow due to severe liver damage, after using a concentrated green-tea extract he bought at a “nutrition” store as a “fat-burning” supplement.

There was concern that he might need a liver transplant but luckily his liver, an organ that has regenerative properties, managed to recover. He did have to give up sporting activities, and will require regular liver function checkups.

Unfortunately this is not an isolated case, and such cases are not limited to green-tea extracts. Recently aegeline, a compound found in the leaves of the Asian bael tree, showed up in supplements marketed as an aid in losing weight and building muscle — despite a lack of any credible evidence. But aegeline may not be without some effect. More than 50 people suffered liver damage, two had to have liver transplants and one died after consuming a supplement containing aegeline.

The multi-hospital-based Drug Induced Liver Injury Network in the U.S. has found that liver problems due to herbal and other dietary supplements have increased three-fold in the last 10 years. Conventional medications still cause far more cases of liver injury, but they also have evidence of efficacy, which is not the case for many herbals.

I suspect that Uncle Gee would have a few devilish words to say about people who might think that they can encapsulate the benefits of Angel tea in a pill. He would likely argue that supplements cannot replicate the same rejuvenating effects he experiences from his daily tea regimen.

I must admit he did look robust and way younger than 84.

But when pushed, he did tell me that he runs six miles three times a week, and can bench press 110 pounds.

So maybe it’s not only the tea that’s keeping him young.

Joe Schwarcz

Thomas Donaldson and cryonics

Screen Shot 2014-09-28 at 12.32.34 PMMost people would like to keep their heads. But don’t count Thomas Donaldson among them. This mathematician and computer consultant wanted his cut off.  And he wanted it to be done while he was still alive. In one of the most bizarre court cases in history, Donaldson petitioned the State of California to allow him to be anesthetized and then be frozen solid with liquid nitrogen. He then wanted his head removed and placed in a stainless steel thermos bottle while the rest of his body was discarded.

Donaldson was not mad, not completely anyway. In the 1970s he had become interested in cryonics, the study of the behavior of matter at low temperatures. He had read about the potential of frozen tissues to be thawed out for future use and when he heard of a company that was looking for people to be frozen with hopes of future resuscitation, he jumped. Alcor was founded in the 1970s in California, where else, with hopes of enlisting people who would be flash frozen after death and stored in liquid nitrogen until technology evolved to the degree that not only could they be brought back to life, but whatever disease they died of, could be cured. In 1975 Donaldson signed up for the program. Unfortunately, thirteen years later he was diagnosed with an inoperable brain tumor. He concluded that if he waited to die, his brain would be so ravaged by the tumor that any hope of bringing him back to life at some future date would be lost. But if he were immediately frozen, the tumor would be stopped in its tracks.

Only his head needed to be kept, Donaldson maintained, because by the time he would be “reanimated” scientists would easily be able to clone the rest of his body from his cells. The only problem was that the authorities made it clear that any technician who took part in this weird experiment would be charged with murder. Hence Donaldsons’s court petition to allow himself to be frozen. It was his constitutional right, he claimed, to determine when and how he would die. The court did not agree and neither did the California Superior court which denied the petition. So Donaldson grumbled and waited to die, which he did in 2006. His body was frozen and now is stored in a cryogenic container at Alcor. As far as we know his head is still attached. That’s unlike baseball great Ted Williams whose head sits in a neighbouring much smaller container…

 

Joe Schwarcz

Diet, Hygiene and Alzheimer’s Disease

cocoa extractThe incidence of Alzheimer’s Disease varies widely around the world. There are far more cases diagnosed in Europe and North America than in Africa, Asia or India. The question is why. Is it genetics? Some difference in lifestyle? Or is the disease just underreported in developing countries? India has a low rate of Alzheimer’s but with less access to physicians and fewer tests available it is possible that many cases of Alzheimer’s are not being recognized as such.

Genetics is not likely to account for the pattern of Alzheimer’s around the globe. For example, Asians who have grown up in North America have the same rate of Alzheimer’s as other Americans. Nigerians in the U.S. experience a higher rate than Nigerians in Africa. In Japan, a country that has traditionally had a low rate of dementia, Alzheimer’s has been increasing significantly. This obviously cannot be attributed to a change in genetics, so it seems that some sort of lifestyle factor that distinguishes poorer and wealthier countries is at play. Diet would seem to be a prime candidate because of significant differences in what people consume around the world. Rice is a staple in most developing countries and is far less widely consumed in the West. Meat, on the other hand, is a western institution. Could it be that the fat content, or the cholesterol, or the iron in meat somehow predispose to Alzheimer’s? In Japan, the incidence of the disease appears to have increased in step with a increase in meat consumption and a decrease in rice consumption. That could mean that rice has some protective factor, or that something in meat is a problem or it could mean nothing.

Epidemiological studies cannot distinguish between associations and cause and effect relationships. For example, there is a highly significant correlation between the divorce rate in the state of Maine and the per capita consumption of margarine. Interesting, but in all likelihood meaningless. There is also a correlation between strict hygiene and sanitation methods as practiced in wealthy countries and the prevalence of Alzheimer’s Disease. Could that be meaningful? In countries with access to clean drinking water the incidence of Alzheimer’s is increased and in countries with a low rate of infectious disease such as Switzerland or Iceland the rates of Alzheimer’s are higher by some 12% than in China and Ghana, both countries with high rates of infectious disease. Is this some spurious correlation or is it meaningful?

The “hygiene hypothesis” is gaining traction when it comes to allergies and asthma with the theory being that exposure to bacteria, viruses and worms early in life primes the development of a healthy immune system. In the absence of exposure to organisms that can actually cause disease, the immune system targets innocent bystanders such as certain food components. Maybe, some researchers suggest, the deposition of proteins in the nervous system, one of the hallmarks of Alzheimer’s, is a result of an immune system that has gone astray. Sounds pretty far fetched, but the absence of any proven cause of Alzheimer’s makes for all sorts of half-baked theories being hatched.

Joe Schwarcz

Souvenaid

souvenaidI suspect we will soon be hearing a lot about “Souvenaid,” a dietary supplement that is supposed to be of some help in the early stages of Alzheimer’s Disease. It was developed by Dr. Richard Wurtman of MIT, a very reputable researcher and the formulation of Souvenaid is based on legitimate science, but unfortunately the evidence for its effectiveness is virtually negligible.

In Alzheimer’s there is a loss of synapses, the connections between nerve cells that form when protrusions develop in cell membranes and reach out towards neighbouring nerve cells. The theory is that providing nutrients needed for healthy cell membranes encourages the formation of new synapses to compensate for the experienced loss.

Souvenaid provides a range of nutrients that include including omega-3 fatty acids (EPA and DHA), phospholipids, choline, uridine monophosphate, vitamins E, C, B12, B6, folic acid and selenium based on the theory that these are needed for the synthesis of phosphatidylcholine, a major constituent of synaptic membranes. The more phosphatidylcholine in cell membranes, the greater the likelihood of synapse formation, at least so goes the theory. But a theory needs evidence to back it up if it is to evolve into practical recommendations. And that evidence is not forthcoming. It isn’t for lack of effort.

A number of studies have been carried out on Alzheimer’s patients with Souvenaid using standardized assessment scales. The results are disappointing. There is no evidence of decreasing the rate of cognitive decline or delaying the progression of the disease in any way, but one of the studies offered a slight glimmer of hope. In patients experiencing early Alzheimer’s Disease, who are not yet taking medication, there was an improvement in verbal recall. That isn’t much to hang a hat on, but at least the supplement was tolerated without side effects. Souvenaid is on the market in Europe and Australia but not yet in the US or Canada despite the low level of evidence that is required for selling dietary supplements. My guess is that Souvenaid will not be of much aid in Alzheimer’s Disease.

 

Joe Schwarcz

Phytoceramides

phytoceramide“As seen on the Dr. Oz Show” is a claim that is guaranteed to boost sales for any product. Like the “phytoceramides” glorified by a couple of plastic surgeons on the show. Incorporated into dietary supplements, these plant derived chemicals are supposed to rejuvenate the skin. There’s no magic pill, Dr. Leif Rogers commented, but “this is pretty close.” And after Dr. Oz wondered “why we haven’t used this earlier,” marketers went to work and quickly filled websites with advertisements about how you can “fake a facelift” with phytoceramides. As is often the case, some websites bleated about Dr. Oz’s “phytoceramide scam,” a common ploy to attract an audience to their site which claims that the product shown on the Oz Show is not as good as the “authentic one” that they are selling.

Perhaps the most impactive statement on the show was Dr. Rogers’ claim that phytoceramides had recently been approved by the FDA. This is totally misleading. In the U.S. dietary supplements do not need premarket approval by the FDA, all that is required is a “Dietary Ingredient Notification” describing what is in the product and why it is believed to be safe. That was not a problem in this case because not only do ceramides occur naturally in our skin, they also can be found in a variety of foods that include dairy products, eggs, soybeans, rice, millet, spinach and wheat. The term “phyto” means plant, so “phytoceramides” are ceramides found in plants.

Ceramides are a class of compounds, along with fatty acids, proteins and cholesterol found in the skin’s outer layer, that help retain moisture. By plumping up the skin, moisture can reduce the appearance of wrinkles. Topical ceramides have long been incorporated into moisturizing creams with positive effects but there are all sorts of substances that can be smeared on the skin to prevent moisture loss, ranging from Vaseline and Crisco to snail extracts. They all work in terms of retaining moisture, but the feel on the skin can be very different. The phytoceramide pills seek to circumvent the problem of finding the right topical moisturizer by delivering the ceramides into the skin directly from blood vessels.

Some studies have indeed shown that such delivery is possible but of course the critical question is whether taking phytoceramide supplements has a noticeable effect. There’s plenty of anecdotal evidence and pictures on the web that show spectacular changes but of course it isn’t hard to fake photos. Then there are claims of celebrities using the product, ranging from Ellen DeGeneres to Jennifer Aniston. We are told that they are not allowed to speak about their use pf phytoceramides because they have contracts with other cosmetic companies. Well, if that is the case, how would anyone know they use phytoceramides?

It is possible that these pills may have an effect, however it is doubtful it would be “near magical.” No surprise that Dr. Rogers uses that expression, given that he sells his own brand of phytoceramides, along with a host of other cosmetics., something that was not mentioned on the Oz Show. Dr. Rogers’ did manage to milk his appearance by prominently featuring “as seen on the Dr. Oz Show” on his website where he also promotes the product she sells. Highly unethical to say the least.

 Joe Schwarcz
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